The neuroprotective role of melatonin in a gestational hypermethioninemia model.

Elevated levels of methionine in blood characterize the hypermethioninemia, which may have genetic or non-genetic origin, as for example from high protein diet. Born rats from hypermethioninemic mothers presented cerebral oxidative stress, inhibition of Na+,K+-ATPase, memory deficit and ultrastructure cerebral changes. Melatonin is a hormone involved in circadian rhythm and has antioxidant effects. The aim of this study was to verify the possible neuroprotective effects of melatonin administration in hypermethioninemic pregnant rats on damage to biomolecules (Na+,K+-ATPase, sulfhydryl content and DNA damage index) and behavior (open field, novel object recognition and water maze tasks), as well as its effect on cells morphology by electron microscopy in offspring. Wistar female rats received methionine (2.68 µmol/g body weight) and/or melatonin (10 mg/kg body weight) by subcutaneous injections during entire pregnancy. Control rats received saline. Biochemical analyzes were performed at 21 and 30 days of life of offspring and behavioral analyzes were performed only at 30 days of age in male pups. Results showed that gestational hypermethioninemia diminished Na+,K+-ATPase activity and sulfhydryl content and increased DNA damage at 21 and 30 days of life. Melatonin was able to totally prevent Na+,K+-ATPase activity alteration at 21 days and partially prevent its alteration at 30 days of rats life. Melatonin was unable in to prevent sulfhydryl and DNA damage at two ages. It also improved DNA damage, but not at level of saline animals (controls). Regarding to behavioral tests, data showed that pups exposed to gestational hypermethioninemia decreased reference memory in water maze, spent more time to the center of the open field and did not differentiate the objects in the recognition test. Melatonin was able to prevent the deficit in novel object recognition task. Electron microscopy revealed ultrastructure alterations in neurons of hypermethioninemic at both ages of offspring, whose were prevented by melatonin. These findings suggest that melatonin may be a good neuroprotective to minimize the harmful effects of gestational hypermethioninemia on offspring.

Vitamin D partially reverses the increase in p-NF-κB/p65 immunocontent and interleukin-6 levels, but not in acetylcholinesterase activity in hippocampus of adult female ovariectomized rats.

The aim of this study was to verify the effects of ovariectomy (OVX) and/or vitamin D supplementation (VIT D) on inflammatory and cholinergic parameters in hippocampus, as well as on serum estradiol and VIT D levels of rats. Ninety-day-old female Wistar rats were randomly divided into four groups: SHAM, OVX, VIT D or OVX + VIT D. Thirty days after OVX, VIT D (500 IU/kg/day) was supplemented by gavage, for 30 days. Approximately 12 h after the last VIT D administration, rats were euthanized and hippocampus and serum were obtained for further analyses. Results showed that OVX rats presented a decrease in estradiol levels when compared to control (SHAM). There was an increase in VIT D levels in the groups submitted to VIT D supplementation. OVX increased the immunocontent of nuclear p-NF-κB/p65, TNF-α and IL-6 levels. VIT D partially reversed the increase in p-NF-κB/p65 immunocontent and IL-6 levels. Regarding cholinergic system, OVX caused an increase in acetylcholinesterase activity without changing acetylcholinesterase and choline acetyltransferase immunocontents. VIT D did not reverse the increase in acetylcholinesterase activity caused by OVX. These results demonstrate that OVX alters inflammatory and cholinergic parameters and that VIT D supplementation, at the dose used, partially reversed the increase in immunocontent of p-NF-Kb/p65 and IL-6 levels, but it was not able to reverse other parameters studied. Our findings may help in the understanding of the brain changes that occurs in post menopause period and open perspectives for futures research involving VIT D therapies.